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Nanoparticles for Protection of Cells from Oxidative Stress

Inactive Publication Date: 2010-07-08
UNIV OF FLORIDA RES FOUNDATION INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0018]In accordance with the invention, free radical scavenging particles can be used as agents to increase the numbers of preserved cells in transplantation of cells; to enhance the viability of transplanted organs both prior to transplantation, i.e., during transport and in vivo after transplantation; to enhance viability and / or function of cell based tissue substitutes; to improve cells' or organisms' lifespans; to improve animals' or humans' health; to improve animals' or humans' lifespan; for anti-aging; for anti-inflammation; and cosmetics; and, optionally, can be used in conjunction with other effective agents.

Problems solved by technology

Despite improvements in the management of individuals with type 1 diabetes, the disorder remains a leading cause of blindness, kidney and heart disease, limb amputation, and other disease associated complications.
Despite recent improvements to the procedure, many obstacles remain including the necessity for patients to utilize potentially deleterious immunosuppressive drugs.
One problem may be that the immunosuppressive drugs cannot undo the underlying autoimmune response that originally destroyed a patient's original islets, [4] while another critical issue involves the loss in islet viability and function post-transplantation.
However, exogenous introduction of these enzymes is not beneficial because they cannot be readily taken up by the cells.

Method used

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  • Nanoparticles for Protection of Cells from Oxidative Stress
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  • Nanoparticles for Protection of Cells from Oxidative Stress

Examples

Experimental program
Comparison scheme
Effect test

example 1

Synthesis of Cerium Oxide Nanoparticles

[0088]CeO2 nanoparticles with a particle size of 2-3 nm have been synthesized previously using the reverse micelle method. However, the surfactant sodium bis(2-ethylhexyl) sulphosuccinate (AOT) was used (see, for example, J. Phys.: Condens. Matter, 2001, 13:5269-5283). To improve biocompatibility and reduce potential toxicity of residual surfactant, a bio-surfactant phosphatidylcholine (i.e., soy bean lecithin) was used to form reverse micelles during synthesis. Phosphatidylcholine naturally occurs in cell membranes. Therefore, phosphatidylcholine for reverse micelle formation is expected to reduce the impact of residual surfactants to cell cultures and transplants and the patient. However, large amounts of lecithin have proven detrimental to the success and therefore more than 90% is removed in washing steps. The washing removes both toluene and the lecithin. Furthermore, the as synthesized nanoparticles require colloidal stabilization after r...

example 2

Cellular Uptake of Cerium Oxide Nanoparticles and Reduction of Oxidative Stress

[0092]The inventors have developed several types of nanoparticles, nanoparticle coatings for cell uptake, a method for making these nanoparticles, and have tested them successfully with human islets of Langerhans as well as other mammalian cell lines.

[0093]The present invention pertains to the application of these nanoparticles to diminish oxidative stresses by catalyzing free radicals. This process can take place both intracellularly, and thus benefit the viability and function of the cells, and in solution and thus can be used for a wide variety of industrial applications.

[0094]The data disclosed herein clearly show a reduction in intracellular free radical concentration when these nanoparticles were provided as a supplement to standard culture media.

[0095]The nanoparticles were cerium oxide or cerium oxide-based materials, and are under 20 nm in size. These nanoparticles are well dispersed in solution,...

example 3

Scavenging Role of Ceria Nanoparticles in Murine Islets

[0114]Further studies focus on the findings that certain nanoparticles (cerium oxide) dramatically increased the longevity of neuronal cells in vitro.

[0115]Materials and Methods

[0116]Ceria Nanoparticles. The ceria nanoparticles have and will continue to be engineered by a microemulsion method that ensures monodisperse nanoparticles with control in diameter ranging from 1-100 nm. The inventors will synthesize two sets of particle sizes 1-5 nm and 10-20 nm [10]. Each set will be treated at three different temperatures to control the stoichiometry (Ce3+ / Ce4+ ratio) of the ceria nanoparticles [11]. The particles will be characterized with high resolution (0.014 nm) scanning transmission electron microscopy with elemental contrast (STEM-z) for size and electronic properties (selected area diffraction (SAD) and light scattering techniques for their ensemble properties, as well as Fourier Transform Infrared Spectroscopy (FTIR) and zeta...

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Abstract

The present invention concerns metal oxide semiconductor nanoparticles with free radical scavenging activity, compositions comprising such nanoparticles, methods for their use, and methods for their production. In one aspect, the invention concerns a method for enhancing the survival or viability of transplanted cells, comprising administering an effective amount of metal oxide semiconductor nanoparticles to a target anatomical site of a subject before, during, or after administration of transplant cells to the subject. Preferably, the metal oxide nanoparticle is a cerium oxide (ceria) nanoparticle.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]The present application claims the benefit of U.S. Provisional Application Ser. No. 60 / 860,646, filed Nov. 22, 2006, which is hereby incorporated by reference herein in its entirety, including any figures, tables, nucleic acid sequences, amino acid sequences, and drawings.BACKGROUND OF THE INVENTION[0002]Cell transplantation therapy is a potentially powerful tool in the treatment of diseases for which there are currently no practical cures. Theoretically, the replacement of defective cells by healthy cells offers the possibility of alleviating the devastating symptoms for many such diseases including Parkinson's disease, stroke, Alzheimer's disease, spinal cord injury, type I diabetes, cirrhosis of the liver and factor 8 hemophilia. The success of the “Edmonton protocol”, which resulted in a 100% cure rate for human Type I diabetes following the transplantation of islet allografts (Shapiro, A. M. et al. N Engl J Med, 2000, 343:230-238), at...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K35/12A61K33/24A61K33/244
CPCA01N1/02A01N1/0226A61K9/5115A61K33/24C12N2533/20A61K33/30C12N5/00C12N2531/00C12N2533/14A61K33/245A61K33/244
Inventor SIGMUND, WOLFGANG M.TSAI, YI-YANGCONSTANTINIDIS, IOANNISDORLEY, JENNYOCA-COSSIO, JOSE ANTONIOSWEENEY, CAROL ANNSIMPSON, NICHOLAS EDWARDATKINSON, MARK A.
Owner UNIV OF FLORIDA RES FOUNDATION INC
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